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ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 1  |  Page : 216-221

The feasibility of sentinellymph nodebiopsy after neo-adjuvant chemotherapy in operable breast cancer patients


1 Department of General Surgery, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Surgical Oncology, Tanta Oncology Centre, Tanta, Egypt

Date of Submission06-Aug-2021
Date of Decision19-Aug-2021
Date of Acceptance24-Aug-2021
Date of Web Publication18-Apr-2022

Correspondence Address:
Tarek M Rageh
Department of General Surgery, Faculty of Medicine, Menoufia University, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_137_21

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  Abstract 


Background
Sentinel lymph-node biopsy (SLNB) has been established as the standard management for pathologic evaluation of the axilla in patients with operable breast cancer and clinically negative axilla (cN0). However, whether SLNB should be performed for patients with node-positive disease after neoadjuvant chemotherapy (NAC) is still controversial.
Patients and methods
This is a clinical multiinstitutional prospective study conducted on 340 patients with operable breast cancer selected from the multidisciplinary breast clinic at Menoufia University Hospital and Tanta Oncology Centre to evaluate the suitability of SLNB for patients with node-negative (group A) and node-positive (group B) breast cancer after NAC. The study was performed from October 2016 to October 2020.
Results
The identification rate for SLNB after NAC was 90.45% and the false-negative rate was 12.5%. The sensitivity, specificity, positive predictive value, and negative predictive value were 98, 91, 90, and 93.5%, respectively. The overall accuracy for SLNB after NAC was 95%.
Conclusion
SLNB after NAC has acceptable false-negative rate, identification rate, and lower in both morbidity and cost. Patients with no initially involved nodes (cN0) with a negative SLN after NAC could safely be spared an unnecessary axillary lymph-node dissection with a low risk of relapse.

Keywords: breast cancer, neoadjuvant chemotherapy, sentinel lymph-node biopsy


How to cite this article:
Rageh TM, Elsisi A, Sabry A, Elsheikh E. The feasibility of sentinellymph nodebiopsy after neo-adjuvant chemotherapy in operable breast cancer patients. Menoufia Med J 2022;35:216-21

How to cite this URL:
Rageh TM, Elsisi A, Sabry A, Elsheikh E. The feasibility of sentinellymph nodebiopsy after neo-adjuvant chemotherapy in operable breast cancer patients. Menoufia Med J [serial online] 2022 [cited 2024 Mar 29];35:216-21. Available from: http://www.mmj.eg.net/text.asp?2022/35/1/216/343099




  Introduction Top


In the early 1990s, the concept of sentinel node [sentinel lymph-node biopsy (SLNB)] was introduced. This concept of minimal invasive surgery for the axilla had fewer adverse effects than routine axillary lymph-node dissection (ALND) [1]. SLNB has been established as the routine management for pathologic evaluation of the axilla in patients with operable breast cancer and clinically negative axilla (cN0) who are planned to have surgery first [2].

In the past few years, neoadjuvant chemotherapy (NAC) is gaining interest and becomes widely used in the management of operable breast cancer as it offers the advantage of downstaging the tumor and testing the efficacy of therapy administered to patients [3]. About 20–70% of patients who present with node-positive disease have complete eradication of the disease in the axilla following NAC [4].

So, ALND with removal of negative axillary lymph nodes has not been shown to provide any clinical benefit, and associated with much morbidity such as limb dysfunction, paraesthesia, and lymphedema [5].

The feasibility of SLN detection after NAC remains questionable. Lymphatic drainage from breast tumors to axillary nodes could be impaired by NAC, leading to a decrease in the SLN identification rate (IR) and an increase in the false-negative rate (FNR) [6].

We aim to conduct this multiinstitutional clinical prospective study to assess the accuracy and safety of SLNB after NAC.


  Patients and methods Top


This is a clinical multiinstitutional prospective study conducted on 340 patients with operable breast cancer, selected from Multidisciplinary Breast Clinic at Menoufia University Hospital and Tanta Oncology Centre. Patients are scheduled for NAC from the period between October 2016 and October 2020.

Inclusion criteria: female patients aged more than 18 years with pathologically proved breast cancer, clinical staging (T1–T3, N0–N2, and M0): patients received NAC as pretreatment strategy.

Exclusion criteria: previous ipsilateral axillary or breast surgery, pregnancy, and lack of premanagement axillary assessment.

All patients were reviewed by our multidisciplinary breast team and staged by clinical examination, soft-tissue mammography, computed tomography chest and abdomen, and bone scan when needed. Written informed consent was taken from the all patients. Ethical approval was obtained by Menoufia University Faculty of Medicine's and Tanta Oncology Centre ethics committee according to the Declaration of Helsinki.

Axillary lymph-node assessment was done by clinical examination, axillary ultrasound, and FNAC or true-cut biopsy of suspicious nodes. Any lymph node larger than 1 cm, with irregular cortical thickening and loss of fatty hilum, was biopsied.

Patients were divided into two groups:

  • Group A (N0): it includes 154 patients without a cytological proven axillary lymph-node involvement before NAC, who were allocated into the N0 group.
  • Group B (N1): it includes 186 patients with a cytological proven axillary lymph-node involvement before NAC, who were allocated into the N1 group.


All patients received NAC (anthracycline and taxane) as their primary treatment that was determined by the medical oncology colleagues in both hospitals. After completion of NAC, fit eligible patients will undergo surgical management in the form of lumpectomy or mastectomy and SLNB using Methylene Blue dye method.

Patients allocated in group A (N0) will have a SLNB and frozen section will be done to SLNs. Complementary ALND only in case of SLN mapping failure or SLN involvement. However, patients allocated into group B (N1) will have SLNB and obligatory ALND [Figure 1].
Figure 1: Schematic distribution of the studied patients between the two groups.

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All specimens will be sent to the Pathology Department for histopathological evaluation of the breast tumor, SLNs, and none of the SLNs by routine paraffin section using H/E and immunohistochemistry staining in both groups.

Full pathological data will be recorded: type of the tumor, grade, stage, biological markers (estrogen receptor, PR, KI67, and HER2 neo), number, and status of both SLNs and non-SLNs.

Statistical analysis

The collected data were organized, tabulated, and statistically analyzed using SPSS software (Statistical Package for the Social Sciences, version 21; SPSS Inc., Chicago, Illinois, USA). Data were described using mean and SD and frequencies according to the type of the data (quantitative or categorical, respectively). Categorical variables were compared using χ2 analysis or Fisher exact test. In all tests, data with a P value less than 0.05 were considered statistically significant. The primary outcomes of this study are to determine the IR and the area under the receiver operating characteristic curve was used to calculate FNR and false-predictive value of the studied models.


  Results Top


A total of 340 patients had enrolled in this study from centers, 154 (45.2%) patients in group A and 186 (54.8%) patients in group B.

Twenty-six patients (12 patients in group A and 14 patients in group B) were excluded from the study before surgery because of disease progression, death, and lost to follow-up.

Mean age of the selected patients was 54 ± 7.3 in group A and 49 ± 6.2 in group B.

In group A (N0), 142 patients were eligible for surgery and SLNB, the majority of patients (64.1%) was T2. Regarding tumor histology, 91.5% was invasive ductal carcinoma and 38% was luminal A type (biological character).

In group B (N1), 172 patients were eligible for surgery and SLNB, 51.8% was T3, 85.4% was invasive ductal cancer, and 39% was luminal A type.

In group A (N0), the patient responses after NAC were complete response in 72.5%, partial response in 23.9%, and stable disease in 3.6%.

In group B (N1), the patient responses after NAC were complete response in 40.69%, partial response in 54.65%, and stable disease in 4.66 [Table 1].
Table 1: Patient, tumor, and treatment characteristics of the clinically nodal studied patients

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In group A (N0), IR of SLN was 90.8%, while in group B (N1), the IR was 90.1% with the total IR 90.45%.

In group A (N0), two or more SLNs were identified in 91.4% (120 patients), while in group B (N1), two or more SLNs were identified in 91.3% (157 patients).

In group A (N0), 14 (10.9%) patients of 129 successful identification had metastatic deposits in their SLNs, while these deposits were found in 75 (48.4%) patients of 155 successful identifications in group B [Table 2].
Table 2: Diagnostic characteristic of sentinel lymph node biopsy after neoadjuvant chemotherapy in clinically studied patients

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ALND was done only in 27 patients of group A (14 patients with positive-metastasis SLN and 13 patients with mapping failure). Fourteen (51.8%) patients had positive metastatic deposits in the nonsentinel lymph node. ALND was done in all cases of group B (172 cases), of whom only 81 (47.1%) from 172 ALND had metastasis.

FNR was calculated only in group B where completion of ALND was obligatory in all cases. FNR was found in 10 (12.5%) patients from 80 patients.

In both groups A and B, the overall IR of SLN was 90.45%. The correlation between SLNB and axillary lymph-node metastases had sensitivity of 98%, specificity 91% with positive predictive value about 90%, and negative predictive value of 93.5%. The overall accuracy of SLNB after NAC was 95% [Table 3].
Table 3: Pathological characteristic of nonsentinel lymph node

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The false-negative cases were 10 (12.5%) cases, 80% of them were HER2 neo positive, 90% had partial response after NAC, 50% were estrogen-receptor-positive, and 70% had only one SLN identified [Table 4].
Table 4: Clinicopathologic factors affecting the false-negative rate in group B

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  Discussion Top


SLNB was first introduced in breast cancer surgery by Krag in 1993, and its use became the standard of care in axillary management in cN0 patients with FNR that was 7.3–9.7% in large clinical trials and meta-analyses [7],[8].

In the past, NAC was introduced for locally advanced breast cancer, and now, its use has been expanded in operable early cases with the advantages of downstaging of the tumor, testing the efficacy of drugs, and allowing more conservative surgery for both breast and axilla [9].

This study is a multiinstitutional study conducted in two high-flow oncology centers in Nile Delta of Egypt, and it is done on 340 patients with operable breast cancer and had NAC as primary treatment.

According to the status of pretreatment axillary lymph node, 154 were enrolled in group A (N0) and 186 patients in group B (N1). SLNs were identified in 129 (90.8%) patients in group A and in 155 (90.1%) patients in group B with an overall IR that was 90.45%. The IR is little lower than the ACOSOG Z1071 trial, where 756 patients, including 649 with clinical N1 disease, were enrolled with IR that was 92.9% [10]. This may be attributable to that we use only blue dye in SLN identification. However, our result is higher than other studies like the SENTINA trial where IR was 80.1% [11].

In group A, ALND was only done in 27 patients due to failure of mapping or positive SLNs, and follow-up of the remaining cases (115 patients) was done for 2 years. During the follow-up period, only one case had axillary recurrence, four cases had breast recurrence, and three cases had distant metastasis. In a recent retrospective study by Nogi et al. [12] done on 181 patients with an initially negative axilla, treated with SLN alone after NAC for a T1–T3 breast cancer, no patients experienced an axillary relapse after a median follow-up of 51.1 months. According to these results, this strategy, in patients presented with negative axillary lymph nodes, appears to be accurate and safe with negligible axillary relapse.

The FNR in this study was 12.5% (10/80 patients) and this was only calculated in group B where mandatory ALND was done. This is almost similar to a meta-analysis study done by Xing et al. [13] that revealed an IR of 91%, the FNR was 12% with 88% sensitivity, and higher than the results of a systematic review done by Kelly et al. [14] where the IR was 89.6% and the FNR was 8.4%.

The reasonable IR and FNR in this study, in spite of the low number of SLNs identified, are due to that we used both H and E and IHC staining. This is similar to the results of the FNAC trial, where IHC was mandatory, allowing micrometastatic SLNs to be characterized as a positive SLN. The FNR was reduced from 13.3% without IHC to 8.4% with IHC [15].

In most of the patients in this study, 91.4% (130 patients) in group A, 91.3% (157 patients) in group B, and two or more SLNs were successfully identified. In this study, there is a small number of false-negative cases (10 patients), and we found that majority of them (70%) had only one SLN identified.

The FNR differed according to the number of removed lymph nodes. In the ACOSOG Z1071 trial, FNR was 31.5% when one SLN was removed, 21% when two SLN were removed, and 9.1% when three SLN were removed. In SANTINA trial, the FNR was 24.3% for women with one SLN removed and 18.5% for those with two SLNs removed [11].

In this study, there is a small number of false-negative cases (10 patients) and we found that majority of them (70%) had only one SLN identified. Also, the majority of FNR were 80% HER2 neo positive and 90% had only partial response after NAC, while half of them were ER positive.

Recently, a novel technique was introduced to decrease the FNR of SLNB after NAC by performing targeted axillary dissection. This is a procedure that involves clipping or marking a positive node before the starting of NAC [16]. Several innovative methods have been used to identify this node after NAC, such as marking the axillary lymph node with iodine-125 (MARI), black charcoal, or wire localization [17],[18].

These promising results from different centers of high IR and low FNR of NCCN guidelines have incorporated SLN surgery after NAC as an accepted part of management, stating that if ipsilateral axillary lymph-node biopsy is positive, axilla may be restaged after preoperative systemic therapy with SLN surgery or ALND (category 2B) [19].

There are many limitations in this study: the small number of FNR cases (10 cases), which were insufficient for multiregression analysis, relatively short period of follow-up (2 years), and implementation of blue dye only for SLN identification due to economic difficulty.


  Conclusion Top


SLNB after NAC has acceptable FNR, IR, less invasive than a complete axillary dissection, and lower in both morbidity and cost.

Patients with no initially involved nodes (cN0) with a negative SLN after NAC could safely be spared an unnecessary ALND with a low risk of relapse.

For patients with an initially involved axillary node (cN1) before NAC: in spite of accepted FNR, SLNB could be used in the future after analysis of clinical pathological risk factors of false-negative cases in larger studies, including a large number of patients with long follow-up periods.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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